Does MDMA Have a Role in Clinical Psychiatry?

Like every drug or technology that has therapeutic value, MDMA (3,4-methylenedioxymethamphetamine) has potential risks and benefits. Unlike most other drugs under clinical investigation, MDMA has a complex and controversial history that has delayed dispassionate scientific investigation into its therapeutic use. Fortunately, research efforts are now overcoming the liabilities of this history, and rigorous research that explores whether MDMA has a role in psychopharmacology is under way.

MDMA was synthesized as an intermediate chemical, and it was patented in 1912 by Merck.1 The first published report of MDMA given to patients appeared in 1978, long after the Merck patent had expired. Shulgin and Nichols2 described the effect of MDMA as “an easily controlled altered state of consciousness with emotional and sensual overtones.” Shulgin introduced the compound to colleagues who were therapists, and the use of MDMA as a catalyst to psychotherapy was taken up by a number of psychiatrists and other therapists in the United States. A few favorable reports of its use appeared in the literature, although there were no controlled clinical trials.3,4

MDMA was neither an approved medication nor an illegal substance, but as it was increasingly marketed under the name “ecstasy” and as recreational use grew, it eventually drew the attention of lawmakers. In 1985, the Drug Enforcement Administration (DEA) deemed MDMA a Schedule 1 substance despite the testimony of physicians and the recommendation of an administrative law judge who suggested that it be a Schedule 3 substance.5 Following this decision, clinical research with MDMA was severely curtailed, but in the past several years it has been gaining momentum.

Recent research

A number of phase 1 safety studies have been done in the United States and Europe, and a phase 2 trial was started in Spain but halted for political reasons unrelated to drug safety.6-15 Additional phase 2 trials are under way in the United States and Switzerland and will soon begin in Israel, Jordan, and Canada. With the exception of 1 study of anxiety associated with advanced stage cancer in the United States, these trials are all directed at studying MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD).

It is noteworthy that all of these clinical trials are using MDMA as an adjunct to psychotherapy, rather than as a stand-alone medication. The drug is administered on only 2 or 3 occasions under direct supervision by a psychiatrist and a cotherapist during prolonged psychotherapy sessions, and treatment effects are compared with those of the same therapy without MDMA. The hypothesis that MDMA catalyzes psychotherapy, now being tested with these rigorous study designs, is derived from earlier published reports of the clinical use of MDMA and is consistent with the current understanding of the pharmacology of MDMA.

In 1986, Greer and Tolbert3 published a report on 29 volunteers to whom MDMA had been administered in the presence of a male and a female therapist. The participants reported benefits such as “enhanced self-understanding [and] insight into personal patterns or problems, greater self-confidence or self-acceptance, lowered defenses [while] undergoing a therapeutic emotional process,” and “less negative thoughts or feelings.”

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Acknowledgment—The author thanks Lisa Jerome, PhD, for her thoughtful suggestions about the manuscript as well as her work on the research, and his other fellow researchers, Mark Wagner, PhD, Ann Mithoefer, BSN, and Rick Doblin, PhD.

References

1. Freudenmann RW, Oxler F, Bernschneider-Reif S. The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents. Addiction. 2006;101:1241-1245.

40. Bedi G, Hyman D, de Wit H. Is ecstasy an “empathogen”? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol Psychiatry. 2010;68:1134-1140.